An Extension Study of JR-171-101 Study in Patients With MPS I

• ClinicalTrials.gov Identifier: NCT04453085
• Recruitment Status: Active, not recruiting
• First Posted: July 1, 2020
• Last Update Posted: March 15, 2024
• Sponsor: JCR Pharmaceuticals Co., Ltd.
• Information provided by (Responsible Party): JCR Pharmaceuticals Co., Ltd.

Tracking Information

• First Submitted Date: June 4, 2020
• First Posted Date: July 1, 2020
• Last Update Posted Date: March 15, 2024
• Actual Study Start Date: October 28, 2021
• Estimated Primary Completion Date: April 30, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 4, 2021)

• Number of participants with Adverse Events [ Time Frame: 156 weeks ]
  Adverse events
• Incidence of abnormal laboratory test results [ Time Frame: 156 weeks ]
  Hematology
• Incidence of abnormal laboratory test results [ Time Frame: 156 weeks ]
  Biochemistry
• Incidence of abnormal laboratory test results [ Time Frame: 156 weeks ]
  Serum iron tests
• Incidence of abnormal laboratory test results [ Time Frame: 156 weeks ]
  Urinalysis
• Incidence of abnormal vital signs [ Time Frame: 156 weeks ]
  Pulse rate
• Incidence of abnormal vital signs [ Time Frame: 156 weeks ]
  Body temperature
• Incidence of abnormal vital signs [ Time Frame: 156 weeks ]
  Blood pressure
• Incidence of abnormal vital signs [ Time Frame: 156 weeks ]
  Body weight
• Incidence of abnormal EKG readings [ Time Frame: 156 weeks ]
• Number of participants with Adverse Events [ Time Frame: 156 weeks ]
  Anti-human-α-L-iduronidase antibodies
• Number of participants with Adverse Events [ Time Frame: 156 weeks ]
  Anti-JR-171 antibodies
• Number of participants with Adverse Events [ Time Frame: 156 weeks ]
  Infusion associated reaction (IAR)

Original Primary Outcome Measures (submitted: June 26, 2020)

• Number of participants with Adverse Events [ Time Frame: 5 years ]
  Adverse events
• Incidence of abnormal laboratory test results [ Time Frame: 5 years ]
  Hematology
• Incidence of abnormal laboratory test results [ Time Frame: 5 years ]
  Biochemistry
• Incidence of abnormal laboratory test results [ Time Frame: 5 years ]
  Serum iron tests
• Incidence of abnormal laboratory test results [ Time Frame: 5 years ]
  Urinalysis
• Incidence of abnormal vital signs [ Time Frame: 5 years ]
  Pulse rate
• Incidence of abnormal vital signs [ Time Frame: 5 years ]
  Body temperature
• Incidence of abnormal vital signs [ Time Frame: 5 years ]
  Blood pressure
• Incidence of abnormal vital signs [ Time Frame: 5 years ]
  Body weight
• Incidence of abnormal EKG readings [ Time Frame: 5 years ]
• Number of participants with Adverse Events [ Time Frame: 5 years ]
  Anti-human-α-L-iduronidase
• Number of participants with Adverse Events [ Time Frame: 5 years ]
  Anti-JR-171 antibodies
• Number of participants with Adverse Events [ Time Frame: 5 years ]
  nfusion associated reaction (IAR)

Current Secondary Outcome Measures (submitted: October 4, 2021)

• Change From Baseline in Heparan Sulfate Levels in Cerebrospinal Fluid [ Time Frame: Weeks 26, 52, 104, 156 ]
• Change From Baseline in Dermatan Sulfate Levels in Cerebrospinal Fluid [ Time Frame: Weeks 26, 52, 104, 156 ]
• CSF opening pressure [ Time Frame: Weeks 26, 52, 104, 156 ]
• Change From Baseline in Heparan Sulfate Levels in Urinary [ Time Frame: Weeks 13, 26, 39, 52, 65, 78, 91, 104, 130, 156 ]
• Change From Baseline in Dermatan Sulfate Levels in Urinary [ Time Frame: Weeks 13, 26, 39, 52, 65, 78, 91, 104, 130, 156 ]
• Change From Baseline in Heparan Sulfate Levels in Serum [ Time Frame: Weeks 13, 26, 39, 52, 65, 78, 91, 104, 130, 156 ]
• Change From Baseline in Dermatan Sulfate Levels in Serum [ Time Frame: Weeks 13, 26, 39, 52, 65, 78, 91, 104, 130, 156 ]
• Change From Baseline in Liver Volume [ Time Frame: Weeks 13, 26, 52, 78, 104, 156 ]
• Change From Baseline in Spleen Volume. [ Time Frame: Weeks 13, 26, 52, 78, 104, 156 ]
• Change From Baseline in Echocardiography. [ Time Frame: Weeks 13, 26, 52, 78, 104, 156 ]
  Left ventricular posterior wall thickness
• Change From Baseline in Echocardiography. [ Time Frame: Weeks 13, 26, 52, 78, 104, 156 ]
  interventricular septal thickness
• Change From Baseline in Echocardiography. [ Time Frame: Weeks 13, 26, 52, 78, 104, 156 ]
  left ventricular mass index
• Change From Baseline in Echocardiography. [ Time Frame: Weeks 13, 26, 52, 78, 104, 156 ]
  left ventricular ejection fraction
• Change From Baseline in Echocardiography. [ Time Frame: Weeks 13, 26, 52, 78, 104, 156 ]
  left ventricular ejection fraction,
• Change From Baseline in Echocardiography. [ Time Frame: Weeks 13, 26, 52, 78, 104, 156 ]
  E/A ratio
• Change From Baseline in 6-minute Walk Test Distance. [ Time Frame: Weeks 13, 26, 52, 78, 104, 156 ]
• Changes from baseline in cognitive age equivalent score of neurocognitive testing [ Time Frame: Weeks 52, 104, 156 ]
  Wechsler IQ test or the Bayley scales of infant and toddler development
• Changes from baseline in outcome of adaptive behavioral function [ Time Frame: Weeks 52, 104, 156 ]
  Vineland adaptive behavior scales
• Changes from baseline in outcome of the Brief Visuospatial Memory Test-Revised [ Time Frame: Weeks 13, 26, 52, 78, 104, 130, 156 ]
• Changes from baseline in outcome of the Hopkins Verbal Learning Test-Revised [ Time Frame: Weeks 13, 26, 52, 78, 104, 130, 156 ]
• Changes from baseline in outcome of the Test of Variables of Attention [ Time Frame: Weeks 13, 26, 52, 78, 104, 130, 156 ]
• Changes from baseline in outcome of the Pediatric Quality of Life Inventory Family Impact Module (PedsQL-FIM) [ Time Frame: Weeks 13, 26, 52, 104 156 ]

Original Secondary Outcome Measures (submitted: June 26, 2020)

• Change From Baseline in Heparan Sulfate Levels in Cerebrospinal Fluid [ Time Frame: Weeks 26, 52, 104, every 52 weeks after Week 104 up to 5 years ]
• Change From Baseline in Dermatan Sulfate Levels in Cerebrospinal Fluidcerebrospinal fluid (CSF) [ Time Frame: Weeks 26, 52, 104, every 52 weeks after Week 104 up to 5 years ]
• CSF opening pressure [ Time Frame: Weeks 26, 52, 104, every 52 weeks after Week 104 up to 5 years ]
• Change From Baseline in Heparan Sulfate Levels in Urinary [ Time Frame: Weeks 13, 26, 39, 52, 65, 78, 91, 104, every 26 weeks after Week 104 up to 5 years ]
• Change From Baseline in Dermatan Sulfate Levels in Urinary [ Time Frame: Weeks 13, 26, 39, 52, 65, 78, 91, 104, every 26 weeks after Week 104 up to 5 years ]
• Change From Baseline in Heparan Sulfate Levels in Serum [ Time Frame: Weeks 13, 26, 39, 52, 65, 78, 91, 104, every 26 weeks after Week 104 up to 5 years ]
• Change From Baseline in Dermatan Sulfate Levels in Serum [ Time Frame: Weeks 13, 26, 39, 52, 65, 78, 91, 104, every 26 weeks after Week 104 up to 5 years ]
• Change From Baseline in Liver Volume [ Time Frame: Weeks 13, 26, 52, 78, 104, every 52 weeks after Week 104 up to 5 years ]
• Change From Baseline in Spleen Volume. [ Time Frame: Weeks 13, 26, 52, 78, 104, every 52 weeks after Week 104 up to 5 years ]
• Change From Baseline in Echocardiography. [ Time Frame: Weeks 13, 26, 52, 78, 104, every 52 weeks after Week 104 up to 5 years ]
  Left ventricular posterior wall thickness
• Change From Baseline in Echocardiography. [ Time Frame: Weeks 13, 26, 52, 78, 104, every 52 weeks after Week 104 up to 5 years ]
  interventricular septal thickness
• Change From Baseline in Echocardiography. [ Time Frame: Weeks 13, 26, 52, 78, 104, every 52 weeks after Week 104 up to 5 years ]
  left ventricular mass index
• Change From Baseline in Echocardiography. [ Time Frame: Weeks 13, 26, 52, 78, 104, every 52 weeks after Week 104 up to 5 years ]
  left ventricular ejection fraction
• Change From Baseline in Echocardiography. [ Time Frame: Weeks 13, 26, 52, 78, 104, every 52 weeks after Week 104 up to 5 years ]
  left ventricular ejection fraction,
• Change From Baseline in Echocardiography. [ Time Frame: Weeks 13, 26, 52, 78, 104, every 52 weeks after Week 104 up to 5 years ]
  E/A ratio
• Change From Baseline in 6-minute Walk Test Distance. [ Time Frame: Weeks 13, 26, 52, 78, 104, every 52 weeks after Week 104 up to 5 years ]
• Neurocognitive testing [ Time Frame: Weeks 52, 104, every 52 weeks after Week 104 up to 5 years ]
  Wechsler IQ test or the Bayley scales of infant and toddler development
• Adaptive behavioral function [ Time Frame: Weeks 52, 104, every 52 weeks after Week 104 up to 5 years ]
  Vineland adaptive behavior scales
• Brief Visuospatial Memory Test-Revised [ Time Frame: Weeks 13, 26, 52, 78, 104, every 26 weeks after Week 104 up to 5 years ]
• Hopkins Verbal Learning Test-Revised [ Time Frame: Weeks 13, 26, 52, 78, 104, every 26 weeks after Week 104 up to 5 years ]
• Test of Variables of Attention [ Time Frame: Weeks 13, 26, 52, 78, 104, every 26 weeks after Week 104 up to 5 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Extension Study of JR-171-101 Study in Patients With MPS I
• Official Title: An Extension Study of JR-171-101 Study in Patients With Mucopolysaccharidosis Type I
• Brief Summary: Phase I/II, open label, multicenter, multinational (Japan, Brazil and the US) extension study of JR-171-101 for the treatment of MPS I
• Detailed Description: Patients who have completed the Part2 of JR-171-101 study and fulfill all eligibility criteria can be enrolled in this JR-171-102 study. Until the dose determination in the JR-171-102 study, subjects will intravenously receive either low dose or high dose of JR-171 at the same doses received at Week 12 of the JR-171-101 study. Thereafter, all subjects will be transitioned to the optimal dose determined based on the results of JR-171-101 study.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Mucopolysaccharidosis I

Intervention

Drug: JR-171 (lepunafusp alfa)

JR-171 IV infusion

Study Arms

Experimental: JR-171

Until the dose determination, subjects will intravenously receive either the low dose or high dose of JR-171 (the same dose as at Week 12 of the JR-171-101 study). Thereafter, all subjects will receive the optimal dose of JR-171 determined based on the results of JR-171-101 study.

Intervention: Drug: JR-171 (lepunafusp alfa)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: August 16, 2022): 14
• Original Estimated Enrollment (submitted: June 26, 2020): 15
• Estimated Study Completion Date: April 30, 2025
• Estimated Primary Completion Date: April 30, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients who have completed the Part 2 of JR-171-101 study
• A patient from whom written informed consent can be obtained. If the patient is aged under 18 years (20 years in case of Japan) at the time of assent or willingness to participate in the study cannot be confirmed due to MPS I-related intellectual disability, informed permission from the patient's legally acceptable representative (e.g., his/her parents or guardians) need to be obtained instead of his/her consent. Even in this case, written informed consent should be obtained from the patient, wherever possible
• Female patient or male patient whose co-partners is of child-bearing potential agree to use a medically accepted, highly effective method of contraception, such as spermatocidal gel plus condom, an intrauterine device or oral contraceptives until one month after the final administration.

Exclusion Criteria:

• A patient who is unable to perform the study procedures, except for 6-minute walk test, neurocognitive testing, BVMT-R, HVLT-R, and T.O.V.A.
• Judged by the principal investigator or subinvestigator as being unable to undergo lumbar puncture, including those who have difficulties in taking a position for lumbar puncture due to joint contracture or those who are likely to experience difficulty breathing during the lumbar puncture process
• Judged by the principal investigator or subinvestigator to be ineligible to participate in the study due to a history of a serious drug allergy or hypersensitivity to any drugs
• Otherwise judged by the principal investigator or subinvestigator to be ineligible to participate in the study in consideration of patient's safety

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil, Japan, United States

Administrative Information

• NCT Number: NCT04453085
• Other Study ID Numbers: JR-171-102
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: JCR Pharmaceuticals Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: JCR Pharmaceuticals Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: JCR Pharmaceuticals Co., Ltd.
• Verification Date: March 2024